两个Usher综合征家系的临床表型分析及致病基因位点的初步定位

Analysis of clinical features and the first study of responsible genes for the two Usher syndrome families

目的:分析2个Usher综合征家系USH-001,USH-002的临床表型特征及遗传学特点,对已知致病基因位点进行筛查,确定可能的候选基因。方法:分析USH-001,USH-002家系患者的临床表型特征、系谱特征,利用连锁分析的原理和方法,对12个已知致病基因位点周围的微卫星标记进行扫描,筛选可能的致病基因位点。结果:USH-001,USH-002家系中的患者在10～13岁出现夜盲症状,随年龄增长夜盲逐渐加重,并出现视野逐渐缩窄至管状视野,中心视力下降不明显,眼底周边见骨细胞样色素沉着;患者在儿童期出现双耳听力下降,为非渐进性、中-重度感音神经性耳聋,以高频听力损失为主,前庭功能正常。表型未出现连续遗传的现象。USH-001家系中所有患者的D11S902,D17S785微卫星标记的Allele值完全一致,USH-002家系所有患者的微卫星标记D1S425,D9S1776的Allele值完全一致。结论:USH-001,USH-002家系临床表现符合USH2型,为常染色体隐性遗传家系。USH1C,USH1G可能为USH-001家系的致病基因;USH2A,USH2D可能为USH-002家系的致病基因。

AIM：To analyze the clinical features of the two Usher Syndrome families USH-001 and USH-002,and screening for possible relevant USH gene map locus·METHODS：The clinical and pedigree features of USH-001,USH-002 families were analysed.The short tandem repeat markers around the 12 known USH gene map locus were screened to choose the possible relevant genes by use of the principles and methods of linkage analysis·RESULTS： The phenotypes of the family USH-001 were similar to USH-002,night blindness occurred in 10-13 years old and gradually got worse with age,visual field gradually narrowed to tubular vision,while the decline of visual acuity were not obvious,bone cell-like retinal pigmentation was found in the peripheral retina.Hearing loss in both ears occurred in childhood,it was non-progressive sensorineural hearing loss,with mainly high-frequency hearing loss and normal vestibular function.Their clinical manifestations were consistent with the diagnosis of USH-002.The phenotype did not consecutively transmit.In USH-001 family all the patients shared the same Allele of D11S902 and D17S785 short tandem repeat markers,and all the patients in USH-002 family shared the same Allele of D1S425and D9S1776 markers·CONCLUSION： USH-001 and USH-002 are USH2 families and their genetic forms are autosomal recessive.USH1C and USH1G are likely pathogenic genes for USH-001 family,USH2A and USH2D are likely pathogenic genes for USH-002 family.